Abstract

Despite multimodal treatment, long term outcome for patients with Ewing
sarcoma is still poor. The second “European interdisciplinary Ewing sarcoma research
summit” assembled a large group of scientific experts in the field to discuss their latest
unpublished findings on the way to the identification of novel therapeutic targets and
strategies. Ewing sarcoma is characterized by a quiet genome with presence of an
EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNAsequencing
of recently described Ewing-like sarcomas with variant translocations
identified them as biologically distinct diseases. Various presentations adressed
mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were
presented shedding light on the molecular underpinnings of genetic permissiveness
to this disease uncovering interaction of EWS-FLI1 with recently discovered
susceptibility loci. Epigenetic context as a consequence of the interaction between the
oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as
dominant theme in the discussion of the molecular pathogenesis and inter- and intratumor
heterogeneity of Ewing sarcoma, and the difficulty to generate animal models
faithfully recapitulating the human disease. The problem of preclinical development
of biologically targeted therapeutics was discussed and promising perspectives were
offered from the study of novel in vitro models. Finally, it was concluded that in order
to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing
sarcoma, the community needs a platform to maintain knowledge of unpublished
results, systems and models used in drug testing and to continue the open dialogue
initiated at the first two Ewing sarcoma summits.

Item Type:

Articles

Additional Information:

We thank Anirah Amber and Nuno Andrade for
excellent organization of the meeting. The conference was
supported by the European Union’s Seventh Framework
Programme grants 261743(ENCCA) and 259348 (ASSET).